title: Toggling a conformational switch in Wnt/β-catenin signaling: regulation of Axin phosphorylation. The phosphorylation state of Axin controls its scaffold function in two Wnt pathway protein complexes.
abstract: The precise orchestration of two opposing protein complexes - one in the cytoplasm (β-catenin destruction complex) and the other at the plasma membrane (LRP6 signaling complex) - is critical for controlling levels of the transcriptional co-factor β-catenin, and subsequent activation of the Wnt/β-catenin signal transduction pathway. The Wnt pathway component Axin acts as an essential scaffold for the assembly of both complexes. How the β-catenin destruction and LRP6 signaling complexes are modulated following Wnt stimulation remains controversial. A recent study in Science by He and coworkers reveals an underlying logic for Wnt pathway control in which Axin phosphorylation toggles a switch between the active and inactive states. This mini-review focuses on this and two other recent studies that provide insight into the initial signaling events triggered by Wnt exposure. We emphasize regulation of the β-catenin destruction and LRP6 signaling complexes and propose a framework for future work in this area.
authors.affiliation: Department of Genetics and the Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
authors.forename: Ofelia
authors.initials: O
authors.lastname: Tacchelly-Benites
authors.forename: Zhenghan
authors.initials: Z
authors.lastname: Wang
authors.forename: Eungi
authors.initials: E
authors.lastname: Yang
authors.forename: Ethan
authors.initials: E
authors.lastname: Lee
authors.forename: Yashi
authors.initials: Y
authors.lastname: Ahmed
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D060466:Axin Protein; D051176:beta Catenin
keywords: Axin; LRP6 signaling complex; PP1; Wnt signal transduction; β-catenin destruction complex